This research proposal will focus on the mechanism of desensitization of the human follicle stimulating hormone receptor (hFSHR) using novel approaches which have not yet been applied to this research problem. The long term objectives of this research are to understand the role of receptor desensitization and trafficking in the context of reproductive health, specifically in infertility and contraception. The first aim is to determine if receptor occupancy is required for desensitization by examining phosphorylation of FSHR in cells containing a mixed population of mutant hFSHR which cannot bind hormone and wild type hFSHR. The second aim is to identify in granulosa cells, which expresses hFSHR in vivo, which members of the family of G protein-coupled receptor kinases are present and responsible for phosphorylating hFSHR. The final aim is to use the yeast two-hybrid system to identify proteins which interact with the receptor. Using these three approaches will help to increase the understanding of what factors are required for proper receptor signaling and how that signal is terminated.